The major goal of the laboratory is the thorough elucidation of mechanisms of control of purine biosynthesis at both the enzyme and complex system levels, and of specific metabolic defects and genotypes of gout and other inherited disorders of purine metabolism. The specific aims of this proposal include 1) Further characterization of avian and human PRPP amidotransferase, including quantitative studis of ligand binding, and conformational changes in presence of substrates or inhibitors. 2) Enzymological study of ribose 5-P ainotransferase. 3) Search for additional metabolic subtypes of primary gout among overproducers with possible abnormalities of PRPP synthtase, PRPP amidotransferase, R5p-aminotransferase. 4) evaluation of proposal that hyperactive variants of glutathione reductase are causally related to hyperuricemia through the hexose monophoshate shunt and influence upon rate of PRPP production.